Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, UK.
Department of Psychiatry, Yale School of Medicine, New Haven.
Psychiatr Genet. 2023 Dec 1;33(6):233-242. doi: 10.1097/YPG.0000000000000352. Epub 2023 Sep 19.
While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits.
We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573).
We identified rs9806493, a chromosome 15 variant, that showed a genome-wide significant association ( Z -score = -5.501, P = 3.77 × 10 -8 ) with ASPD criteria. rs9806493 is an eQTL for SLCO3A1 (Solute Carrier Organic Anion Transporter Family Member 3A1), a ubiquitously expressed gene with strong expression in brain regions that include the anterior cingulate and frontal cortices. Polygenic risk score analysis identified positive correlations between ASPD and smoking, ADHD, depression traits, and posttraumatic stress disorder. Negative correlations were observed between ASPD PRS and alcohol intake frequency, reproductive traits, and level of educational attainment.
This study provides evidence for an association between ASPD risk and SLCO3A1 and provides insight into the genetic architecture and pleiotropic associations of ASPD.
虽然在确定反社会行为的遗传基础方面已经取得了进展,但在反社会人格障碍(ASPD)方面却几乎没有进展,ASPD 常与其他精神疾病同时发生,包括物质使用障碍、注意缺陷多动障碍(ADHD)和焦虑障碍。本研究旨在提高对 ASPD 的遗传风险及其与其他疾病和特征的关系的认识。
我们对英国(UCL,N=644)和美国(耶鲁-宾州,N=2573)的 3217 名酒精依赖参与者的 ASPD 诊断标准数据进行了全基因组关联研究(GWAS)。
我们确定了 rs9806493,这是一种 15 号染色体变异,与 ASPD 标准具有全基因组显著关联(Z 分数=-5.501,P=3.77×10 -8 )。rs9806493 是 SLCO3A1(溶质载体有机阴离子转运蛋白家族成员 3A1)的一个 eQTL,SLCO3A1 是一种在大脑区域广泛表达的基因,包括前扣带回和额皮质。多基因风险评分分析发现,ASPD 与吸烟、ADHD、抑郁特征和创伤后应激障碍之间存在正相关。在 ASPD PRS 与饮酒频率、生殖特征和受教育程度之间观察到负相关。
本研究为 ASPD 风险与 SLCO3A1 之间的关联提供了证据,并深入了解了 ASPD 的遗传结构和多效性关联。